Document Detail


Genome-wide association study of the age of onset of childhood asthma.
MedLine Citation:
PMID:  22560479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children.
OBJECTIVE: We sought to identify genetic variants associated with earlier onset of childhood asthma.
METHODS: We conducted the first genome-wide association study of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP) and used 3 independent cohorts from North America, Costa Rica, and Sweden for replication.
RESULTS: Two single nucleotide polymorphisms (SNPs) were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: rs9815663 (Fisher P= 2.31 × 10(-8)) and rs7927044 (P= 6.54 × 10(-9)). Of these 2 SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10(-7) <P< 8.22 × 10(-6)). Having 1 or more risk alleles of the 2 SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP.
CONCLUSIONS: We have identified 2 SNPs associated with earlier onset of childhood asthma in 4 independent cohorts.
Authors:
Erick Forno; Jessica Lasky-Su; Blanca Himes; Judie Howrylak; Clare Ramsey; John Brehm; Barbara Klanderman; John Ziniti; Erik Melén; Goran Pershagen; Magnus Wickman; Fernando Martinez; Dave Mauger; Christine Sorkness; Kelan Tantisira; Benjamin A Raby; Scott T Weiss; Juan C Celedón
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-02
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  130     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-29     Completed Date:  2012-09-17     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  83-90.e4     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Age of Onset
Asthma / epidemiology*,  genetics
Child
Cohort Studies
Costa Rica / epidemiology
Female
Genetic Predisposition to Disease
Genome-Wide Association Study / methods*
Genotype
Humans
Linkage Disequilibrium
Male
North America / epidemiology
Polymorphism, Single Nucleotide / genetics*
Sweden / epidemiology
Grant Support
ID/Acronym/Agency:
HL66289/HL/NHLBI NIH HHS; K01 HL004370/HL/NHLBI NIH HHS; M01RR00051/RR/NCRR NIH HHS; M01RR0099718-24/RR/NCRR NIH HHS; M01RR02719-14/RR/NCRR NIH HHS; N01-HR-16044/HR/NHLBI NIH HHS; N01-HR-16045/HR/NHLBI NIH HHS; N01-HR-16046/HR/NHLBI NIH HHS; N01-HR-16047/HR/NHLBI NIH HHS; N01-HR-16048/HR/NHLBI NIH HHS; N01-HR-16049/HR/NHLBI NIH HHS; N01-HR-16050/HR/NHLBI NIH HHS; N01-HR-16051/HR/NHLBI NIH HHS; N01-HR-16052/HR/NHLBI NIH HHS; N01HR16044/HL/NHLBI NIH HHS; N02-HL-6-4278/HL/NHLBI NIH HHS; R00 HL096840/HL/NHLBI NIH HHS; R01 HL066289/HL/NHLBI NIH HHS; RR00036/RR/NCRR NIH HHS; UL1 TR000427/TR/NCATS NIH HHS; WT084703MA//Wellcome Trust
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